M-CSF-specific monoclonal antibody and uses thereof

Abstract

M-CSF-specific RX1-based or RX-I derived antibodies are provided, along with pharmaceutical compositions containing such antibody, kits containing a pharmaceutical composition, and methods of preventing and treating bone loss in or remodeling in a subject afflicted with an osteoblastic or osteolytic disease.

What is claimed is: 
     
       1. A method of treating a subject suffering from a disease associated with periprosthetic bone loss or increased osteoclastic activity and increased osteoblastic activity comprising administering to the subject a non-murine antibody that competes with monoclonal antibody RX1 for binding to M-CSF by more than 75%, wherein said monoclonal antibody RX1 comprises the heavy chain and light chain amino acid sequences set forth in SEQ ID NOs: 2 and 4, respectively; and wherein the non-murine antibody comprises SEQ ID NOs: 18, 21, 24, 32, 36 and QASQSIGTSIH (SEQ ID NO: 138). 
     
     
       2. The method of  claim 1  wherein the non-murine antibody specifically binds to the same epitope of M-CSF as said monoclonal antibody RX1, said epitope comprising at least 4 contiguous residues of SEQ ID NO: 120 or 121. 
     
     
       3. The method of  claim 1  wherein the non-murine antibody is a monoclonal antibody. 
     
     
       4. The method of  claim 1  wherein the non-murine antibody is a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, or a single chain antibody. 
     
     
       5. The method of  claim 1  wherein the non-murine antibody retains an affinity Kd with respect to M-CSF of SEQ ID NO: 9 of at least 10-8 M or higher. 
     
     
       6. The method of  claim 1  wherein the non-murine antibody comprises a constant region of a human antibody sequence and one or more heavy and light chain variable framework regions of a human antibody sequence. 
     
     
       7. The method of  claim 6  wherein the human antibody sequence is an individual human sequence, a human consensus sequence, an individual human germline sequence, or a human consensus germline sequence. 
     
     
       8. The method of  claim 1  wherein the non-murine antibody comprises a fragment of an IgG1 constant region. 
     
     
       9. The method of  claim 8  wherein the non-murine antibody comprises a mutation in the IgG1 constant region that reduces antibody-dependent cellular cytotoxicity or complement dependent cytotoxicity activity. 
     
     
       10. The method of  claim 1  wherein the non-murine antibody comprises a fragment of an IgG4 constant region. 
     
     
       11. The method of  claim 10  wherein the non-murine antibody comprises a mutation in the IgG4 constant region that reduces formation of half-antibodies. 
     
     
       12. The method of  claim 1  further comprising administering a second therapeutic agent. 
     
     
       13. The method of  claim 1  wherein the antibody is administered at a dose between about 0.1 mg/kg to 30 mg/kg body weight.